PMID- 21614172
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20110630
LR  - 20211020
IS  - 1347-5800 (Electronic)
IS  - 0044-5991 (Print)
IS  - 0044-5991 (Linking)
VI  - 44
IP  - 2
DP  - 2011 Apr 28
TI  - Analysis of mTOR inhibition-involved pathway in ovarian clear cell 
      adenocarcinoma.
PG  - 113-8
LID - 10.1267/ahc.10029 [doi]
AB  - This study was designed to clarify the mechanism of the mammalian target of 
      rapamycin (mTOR)-hypoxia inducible factor-1 (HIF-1) pathway using the cultured 
      cell strain derived from human ovarian clear cell adenocarcinoma (CCA). 
      Everolimus (a derivative of rapamycin)-treated cells and non-treated cells did 
      not show any difference in mTOR expression. But, phosphorylated-mTOR (p-mTOR) 
      expression significantly decreased in the treated cells, and mTOR-related factors 
      such as phosphorylated-4E-BP1 (p-4E-BP1), HIF-1alpha, and vascular endothelial growth 
      factor (VEGF) in the downstream region of mTOR revealed a marked decrease in 
      expression. The analysis of influences of the drug on the HIF-1alpha degradation 
      system showed an increase in von-Hippel Lindau (VHL) expression in the treated 
      cells. Increase of cleaved caspase-3, one of key factors involved in apoptosis, 
      was also shown in the treated cells. In the next step, using nude mice implanted 
      with RMG-1 cells, a decrease in tumor size was demonstrated in 4 of the 7 mice 
      which were orally administered with everolimus. As a result, it was suggested 
      that everolimus administration would be helpful as an anti-tumor therapy for CCA 
      not only via down-regulation of p-mTOR but also degradation of HIF-1alpha by VHL and 
      induction of apoptosis by cleaved caspase-3.
FAU - Harasawa, Makiko
AU  - Harasawa M
AD  - Department of Obstetrics and Gynecology, Tokai University School of Medicine.
FAU - Yasuda, Masanori
AU  - Yasuda M
FAU - Hirasawa, Takeshi
AU  - Hirasawa T
FAU - Miyazawa, Masaki
AU  - Miyazawa M
FAU - Shida, Masako
AU  - Shida M
FAU - Muramatsu, Toshinari
AU  - Muramatsu T
FAU - Douguchi, Kensho
AU  - Douguchi K
FAU - Matsui, Naruaki
AU  - Matsui N
FAU - Takekoshi, Susumu
AU  - Takekoshi S
FAU - Kajiwara, Hiroshi
AU  - Kajiwara H
FAU - Yoshiyuki Osamura, R
AU  - Yoshiyuki Osamura R
FAU - Mikami, Mikio
AU  - Mikami M
LA  - eng
PT  - Journal Article
DEP - 20110421
PL  - Japan
TA  - Acta Histochem Cytochem
JT  - Acta histochemica et cytochemica
JID - 0147110
PMC - PMC3096079
OTO - NOTNLM
OT  - anti-cancer therapy
OT  - clear cell carcinoma
OT  - mTOR
OT  - ovary
OT  - rapamycin
EDAT- 2011/05/27 06:00
MHDA- 2011/05/27 06:01
PMCR- 2011/04/28
CRDT- 2011/05/27 06:00
PHST- 2010/11/08 00:00 [received]
PHST- 2011/02/25 00:00 [accepted]
PHST- 2011/05/27 06:00 [entrez]
PHST- 2011/05/27 06:00 [pubmed]
PHST- 2011/05/27 06:01 [medline]
PHST- 2011/04/28 00:00 [pmc-release]
AID - AHC10029 [pii]
AID - 10.1267/ahc.10029 [doi]
PST - ppublish
SO  - Acta Histochem Cytochem. 2011 Apr 28;44(2):113-8. doi: 10.1267/ahc.10029. Epub 
      2011 Apr 21.